Il-31 Does not Correlate to Pruritus Related to Early Stage Cutaneous T-cell Lymphomas but is Involved in Pathogenesis of the Disease

Abstract

Mycosis fungoides (MF) and Sézary syndrome (SS) belong to the group of primary cutaneous T-cell lymphomas (CTCL). Regardless of the stage of the disease, patients with MF and SS can suffer from chronic pruritus. The aim of the study was to investigate the correlation between the interleukin 31 (IL-31) serum level, the degree of pruritus and CTCL severity; and to compare the frequency of IL-31 gene polymorphisms between patients and the control group, and between patients at different stages of the disease. Pruritus affected 67.7% of patients with MF and SS in our study. The IL-31 serum level was significantly higher in CTCL patients than in the control group but there were no positive correlation between IL-31 serum level and pruritus. A statistically significant difference in allele frequencies for IL-31 IVS2+12 gene polymorphisms between early and advanced stages was detected; GAG haplotype was more frequent and AGA was less frequent in stage IA patients compared with patients in the other stages of the disease.

Pruritus Reduction with Systemic Anti-lymphoma Treatments in Patients with Cutaneous T Cell Lymphoma: A Narrative Review

“…However, the pathophysiology of CTCL-related pruritus remains unclear. Patients with CTCL may experience pruritus on skin lesions or uninvolved skin, even before other skin-related symptoms manifest [6, 16, 30]. These observations suggest that a soluble pruritic factor could be generated locally at the diseased skin or elsewhere in the body [16].…”

“…These observations suggest that a soluble pruritic factor could be generated locally at the diseased skin or elsewhere in the body [16]. CTCL-related pruritus does not typically respond well to anti-histamine treatments, suggesting that mediators other than histamine may be involved [30, 31]. …”

“…Reports have shown that patients with CTCL-related pruritus also had higher levels of IL-31 than those without and resolution of pruritus correlated with a decrease in IL-31 [36]. In another study, levels of IL-31 and severity of pruritus were correlated for patients with stage IB CTCL [30]. Interestingly, in vitro treatment of peripheral mononuclear blood cells (PBMCs) from patients with stage III-IV CTCL with vorinostat or dexamethasone suppressed production of IL-31.…”

Malignancy‐associated pruritus

“…Given the correlation of IL-31 to pruritic skin lesions and CTCL, a recent casecontrol study set out to determine if IL-31 serum levels correlated with the presence of itch in CTCL patients. However, a previous study did not find a link between serum levels of IL-31 and itch intensity in patients with early stage CTCL (Malek et al, 2015). A subsequent study found that reducing IL-31 using histone deacetylase inhibitors, prednisone or anti-CCR4 monoclonal antibodies in advanced stage CTCL patients significantly reduced pruritus (Cedeno-Laurent et al, 2015).…”

Paraneoplastic Itch: An Expert Position Statement from the Special Interest Group (SIG) of the International Forum on the Study of Itch (IFSI)

“…Recent data demonstrated that prednisone reduces IL-31 expression in malignant T cells and this is correlated to reduced itch in cutaneous T-cell lym phoma (CTCL) patients (34). However, a more recent study (39) failed to find a correlation between IL-31 levels in serum and itch severity in patients with CTCL.…”